The impact of isomerism of pyrimidine-based ligands and their rhodium(III) complexes with regard to their structures and properties was investigated. Two isomeric ligands, 4-(3,5-dimethyl-1H-pyrazol-1-yl)-2,5-diphenylpyrimidine (HL^2,5) and 4-(3,5-dimethyl-1H-pyrazol-1-yl)-2,6-diphenylpyrimidine (HL^2,6), were synthesized. The ligands differ by the degree of steric bulk: the molecular structure of HL^2,5 is more distorted due to presence of pyrazolyl and phenyl groups in the neighbouring positions 4 and 5 of the pyrimidine ring. The complexation of HL^2,5 and HL^2,6 with RhCl₃ leads to the sp² C–H bond activation, resulting in the isolation of two complexes, [RhL^2,5(Solv)Cl₂]·nEtOH and [RhL^2,6(Solv)Cl₂]·nEtOH (Solv = H₂O, EtOH), with the deprotonated forms of the pyrazolylpyrimidine molecules which coordinate the Rh³⁺ ion as N^N^C-tridentate ligands. According to DFT modelling, the mechanism of the deprotonation involves (i) the C–H bond breaking in the 2-phenyl group followed by the coordination of the C atom to the Rh atom, (ii) the protonation of coordinated chlorido ligand, (iii) the ejection of the HCl molecule and (iv) the coordination of the H₂O molecule. The ligand isomerism has an impact on emission properties and cytotoxicity of the complexes. Although the excited states of the complexes effectively deactivate through S₀/T₁ and S₀/S₁ crossings associated with the cleavage of the weak H₂O ligands upon excitation, the [RhL^2,5(Solv)Cl₂]·nEtOH complex appeared to be emissive in the solid state, while [RhL^2,6(Solv)Cl₂]·nEtOH is non-emissive at all. The complexes show significant cytotoxic activity against cancerous HepG2 and Hep2 cell lines, with the [RhL^2,6(Solv)Cl₂]·nEtOH complex being more active than its isomer [RhL^2,5(Solv)Cl₂]·nEtOH. On the other hand, noticeable cytotoxicity of the latter against HepG2 is supplemented by its non-toxicity against non-cancerous MRC-5 cells.

中文翻译：

---

N^N^C-环金属化铑(III)与异构嘧啶基配体的配合物：揭示异构现象对结构基序、发光和细胞毒性的影响

研究了嘧啶基配体及其铑( III )配合物的异构现象对其结构和性能的影响。两个异构配体，4-(3,5-二甲基-1 H -吡唑-1-基)-2,5-二苯基嘧啶 ( HL ^2,5 ) 和 4-(3,5-二甲基-1 H -吡唑-1)合成了-yl)-2,6-二苯基嘧啶( HL ^2,6 )。配体的空间体积程度有所不同：由于嘧啶环的相邻位置 4 和 5 上存在吡唑基和苯基，HL ^2,5的分子结构更加扭曲。 HL ^2,5和HL ^2,6与 RhCl ₃的络合导致 sp ² C–H 键活化，从而分离出两个络合物：[RhL ^2,5 (Solv)Cl ₂ ]· n EtOH和[ RhL ^2,6 (Solv)Cl ₂ ]· n EtOH (Solv = H ₂ O, EtOH)，具有吡唑基嘧啶分子的去质子化形式，其将Rh ³⁺离子配位为N^N^C-三齿配体。根据DFT模型，去质子化的机制涉及（i）2-苯基中的C-H键断裂，然后C原子与Rh原子配位，（ii）配位氯配体的质子化，（ iii) HCl 分子的喷射和(iv) H ₂ O 分子的配位。配体异构现象对配合物的发射特性和细胞毒性有影响。尽管复合物的激发态通过与弱 H ₂ O 配体在激发时裂解相关的S ₀ /T ₁和 S ₀ /S ₁交叉有效失活， [RhL ^2,5 (Solv)Cl ₂ ]· n EtOH络合物在固态下似乎具有发射性，而[RhL ^2,6 (Solv)Cl ₂ ]· n EtOH根本不具有发射性。该复合物对癌性 HepG2 和 Hep2 细胞系表现出显着的细胞毒活性，其中[RhL ^2,6 (Solv)Cl ₂ ]· n EtOH复合物比其异构体[RhL ^2,5 (Solv)Cl ₂ ]· n活性更高乙醇。另一方面，后者对 HepG2 的显着细胞毒性与其对非癌性 MRC-5 细胞的无毒性相补充。